Over the past decades, research and development activities in the pharmaceutical industry have lead to the discovery of thousands of new molecules and chemical structure motifs that have a strong potential to be used in the treatment of human diseases; yet only a small proportion of these lead candidates have made it to the market. Increasingly, low solubility and complex polymorphism of lead molecules limit the suitability of these molecules, and a number of products based on such molecules are failing just before introduction to the market. At the same time, the number of recalls of products on the market due to problems originating from their physico-chemical properties is on the rise.
One very promising approach to increase the solubility of a pharmaceutical is to formulate the molecules of the pharmaceutical into an amorphous phase, which is higher in energy than the crystalline state and hence intrinsically tends to exhibit higher solubility. It is fairly straightforward to make drug molecules amorphous and an associated increase in bioavailability for an amorphous drug compared to its crystalline counterparts has been demonstrated. However, the amorphous state is thermodynamically unstable and currently it is impossible to predict whether or not an amorphous drug will be stable over the shelf life of the drug product. This problem means that the commercial application of the strategy of making drug molecules amorphous is currently extremely limited.
Similar problems arise in fields other than pharmaceuticals, such as in relation to foods, cosmetics, consumer chemicals, paints and the like, in which performance enhancements may be gained by using molecules in an amorphous form but in which the stability of the amorphous form cannot be predicted.